Journal of Antimicrobial Chemotherapy最新文献

{"title":"Mechanisms of resistance to ceftazidime/avibactam in mutants derived in vitro from Klebsiella pneumoniae producing OXA-48-like enzymes.","authors":"T Blanco-Martín, J Guzmán-Puche, M Hernández-García, M Muñoz-Rosa, C Elías-López, C Riazzo, J Torre-Cisneros, J Arca-Suárez, M Causse, G Bou, R Cantón, L Martínez-Martínez","doi":"10.1093/jac/dkaf360","DOIUrl":"https://doi.org/10.1093/jac/dkaf360","url":null,"abstract":"<p><strong>Objectives: </strong>To generate in vitro ceftazidime-avibactam-resistant mutants derived from Klebsiella pneumoniae producing OXA-48 or OXA-48 derivatives OXA-131 and OXA-232 carbapenemases, to define their antimicrobial susceptibility phenotype and to analyse mutations potentially involved in resistance to ceftazidime-avibactam.</p><p><strong>Methods: </strong>Mutants were obtained by plating overnight bacterial cultures on Mueller-Hinton agar plates containing increasing concentrations of ceftazidime-avibactam (0.5/4-32/4 mg/L). MICs were determined using Sensititre™ DKMNG panels. Whole-genome sequencing of 8 parental strains and 31 mutant derivatives was performed with Illumina.</p><p><strong>Results: </strong>All parental strains were susceptible to ceftazidime-avibactam (MIC ≤ 0.5/4-2/4 mg/L) and either susceptible or resistant to meropenem (MIC 0.5 to >16 mg/L) and imipenem (MIC ≤ 0.5 to >16 mg/L). MICs of ceftazidime-avibactam for the mutants increased up to 4 to >16 mg/L, while MICs of meropenem and imipenem for most mutants either increased up to >16 mg/L or remained unchanged. Whole-genome sequencing of the mutants identified alterations in genes coding for proteins related to AcrAB-TolC (AcrB, AcrR), PBPs (PBP2, PBP3), porins (OmpK36, EnvZ) or the stress or stringent responses (RseB, CpxA, SpoT). No mutations were detected in genes coding for OXA-48-like enzymes or other β-lactamases.</p><p><strong>Conclusions: </strong>Ceftazidime-avibactam can select in vitro mutants of OXA-48-like carbapenemase-producing K. pneumoniae resistant to this combination and, in some cases, also to carbapenems. No mutations related to ceftazidime-avibactam resistance were found in genes coding OXA-48-like enzymes, but they were detected in genes related to active efflux, PBPs, permeability or proteins of the stress and stringent responses.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving landscape of methicillin-resistant Staphylococcus pseudintermedius: the emergence of new epidemic waves across Europe, Asia and North America.","authors":"Lillian Rose Giarratana, Mattia Pirolo, Franz-Ferdinand Roch, Beate Conrady, Luca Guardabassi","doi":"10.1093/jac/dkaf340","DOIUrl":"https://doi.org/10.1093/jac/dkaf340","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify spatiotemporal variations in clonal diversity and antimicrobial resistance of methicillin-resistant Staphylococcus pseudintermedius (MRSP).</p><p><strong>Materials and methods: </strong>A PubMed search (June 2016-December 2023), combined with data from PubMLST and a previous review (September 2007-May 2016), identified 2654 isolates. Multinomial logistic regression (MLR) and Bayesian regression models (BRMs) were used to assess associations between clonal complexes (CCs) and variables (sample type, continent and period), with MLR results feeding into the BRM.</p><p><strong>Results: </strong>A shift in MRSP clonal structure was observed after 2013. A decline in the prevalence of historically dominant lineages, such as CC71 in Europe, CC68 in North America and CC45 in Asia, coincided with the global emergence of CC551, as well as CC556 and CC1431 in North America, and CC363 and CC1631 in Asia. Resistance to non-β-lactams increased in North America, particularly for chloramphenicol (6%-59%), remained largely stable in Europe except for tetracycline, and decreased in Asia. Striking differences among CCs were observed, with CC71 exhibiting the highest resistance rates and a greater likelihood of being isolated from clinical samples.</p><p><strong>Discussion: </strong>The observed associations between specific CCs and resistance patterns provide valuable insights into the factors driving these epidemiological changes, including regional antimicrobial use patterns (e.g. chloramphenicol usage in North America) and potential fitness advantages of emerging lineages. These dynamics parallel those seen in methicillin-resistant Staphylococcus aureus.</p><p><strong>Conclusion: </strong>The evolving MRSP landscape highlights the need for sustained global surveillance to monitor clonal diversity, antimicrobial use and resistance trends.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of disc diffusion and broth microdilution methods for aztreonam/avibactam susceptibility testing in Enterobacterales.","authors":"Ioannis Baltas, Deny Tsakri, Sofia Vourli, Himani Solanki, Evelyn Murrell, Eftychia Kiousi, Zacharias Tsakris, Gabriella Kuczmar, Nikoletta Smyrni, Ioannis Skiadas, Vassilios Grammelis, James Hatcher, Damianos Menegas, Athanasios Tsakris, Georgia Vrioni, Louis Grandjean","doi":"10.1093/jac/dkaf361","DOIUrl":"https://doi.org/10.1093/jac/dkaf361","url":null,"abstract":"<p><strong>Background: </strong>Aztreonam/avibactam is a novel β-lactam/β-lactamase inhibitor (BL/BLI) combination active against carbapenem-resistant Enterobacterales (CRE), including MBL-producing isolates. In May 2024, EUCAST published Enterobacterales breakpoints for aztreonam/avibactam. This study aimed to assess the performance of commercially available disc diffusion (DD) against broth microdilution (BMD) using the latest EUCAST breakpoints.</p><p><strong>Methods: </strong>We tested 278 CRE causing infections in 17 Greek ICUs between 2021 and 2023, using 30/20 μg aztreonam/avibactam discs and BMD according to EUCAST methodology and EUCAST version 15.0 breakpoints.</p><p><strong>Results: </strong>Most isolates were identified as Klebsiella pneumoniae (97.8%), and 98.9% produced carbapenemases, including 46.4% KPC, 20.1% NDM, 5.4% VIM and 27% multiple carbapenemases. Using BMD, 94.2% of isolates were susceptible to aztreonam/avibactam. Conversely, using DD, 66.9% were susceptible, 33.1% resistant and 27% within the area of technical uncertainty (ATU). Most isolates in the ATU were KPC-producing (68%) or KPC and MBL-producing (29.3%). All isolates in the ATU (22-24 mm) tested susceptible by BMD (MIC ≤ 4 mg/L). One isolate exhibited resistance by DD (20 mm), but was susceptible by BMD. Categorical agreement (CA) was 72.7%, with 29% major errors (MEs) and 0% very major errors (VMEs). Using a breakpoint of 22 mm, CA, ME and VME were 99.6%, 0.4% and 0%, respectively.</p><p><strong>Conclusions: </strong>Aztreonam/avibactam showed potent in vitro activity against MBL- and KPC-producing Enterobacterales. Using the 2025 EUCAST breakpoint, all isolates in the ATU tested susceptible by BMD, leading to high MEs of the DD method. A 22 mm breakpoint would have corrected this discrepancy in our cohort.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dalbavancin dosing in a severely underweight woman with prosthetic valve endocarditis: the critical role of proactive therapeutic drug monitoring.","authors":"Ambra Barco, Dario Cattaneo, Jessica Cusato","doi":"10.1093/jac/dkaf365","DOIUrl":"https://doi.org/10.1093/jac/dkaf365","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of an LC coupled with tandem MS (LC-MS/MS) tool in the detection of antimicrobial resistance mechanisms in Enterobacterales.","authors":"Anna Witkowska, Marta Biedrzycka, Radosław Izdebski, Elżbieta Literacka, Paweł Urbanowicz, Francis Deforet, Romain Carrière, Frédéric Robin, Elżbieta U Stolarczyk, Jérôme Lemoine, Marek Gniadkowski","doi":"10.1093/jac/dkaf339","DOIUrl":"https://doi.org/10.1093/jac/dkaf339","url":null,"abstract":"<p><strong>Objectives: </strong>To assess a new MS approach in detection of antimicrobial resistance (AMR) mechanisms in Enterobacterales and its usefulness in the routine practice of a national reference centre for carbapenemase-producing enterobacteria (CPE).</p><p><strong>Methods: </strong>A tool utilizing LC coupled with tandem MS (LC-MS/MS) in multiple reaction monitoring mode was tested in the direct and concurrent detection of 13 AMR enzymes. These comprised carbapenemases, extended-spectrum β-lactamases (ESBLs), AmpC-like cephalosporinases, aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methylases. The study included 357 Enterobacterales isolates largely from Polish hospitals (2000-23), including 292 CPE, collected by the National Reference Centre for Susceptibility Testing. The isolates were short-read sequenced to determine their resistomes, and subjected to MIC evaluation.</p><p><strong>Results: </strong>The number of target AMR genes in the isolates was 1128 without defective and duplicated copies. When possible to deduce, the MIC patterns indicated activity of most of the genes/enzymes. The LC-MS/MS assay showed >95% sensitivity in the identification of KPC-, NDM-, VIM-, IMP- and OXA-48-type carbapenemases, CTX-M-like ESBLs, CMY-2- and DHA-type AmpCs, Aac(3)-II- and Aac(6')-Ib-like AMEs and the ArmA 16S rRNA methylase, but only 66.7% and 44.4% of GES-type ESBLs/carbapenemases and RmtB/C-like methylases, respectively. Detection specificity was almost 100% for all of the enzymes.</p><p><strong>Conclusions: </strong>The study demonstrated good performance of the assay against multiple clinically-relevant AMR mechanisms, including main carbapenemase types, and its usefulness in a CPE reference centre was confirmed. However, further studies, e.g. with other bacterial populations, AMR mechanisms and clinical samples, are necessary to characterize its full diagnostic potential.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of commonly used antibiotics on children's developing gut microbiomes and resistomes in peri-urban Lima, Peru.","authors":"Neha Sehgal, Monica J Pajuelo, Robert H Gilman, Amy J Pickering, Ashlee M Earl, Colin J Worby, Maya L Nadimpalli","doi":"10.1093/jac/dkaf358","DOIUrl":"10.1093/jac/dkaf358","url":null,"abstract":"<p><strong>Background: </strong>The effects of antibiotic use on children's gut microbiomes and resistomes are not well characterized in middle-income countries, where antibiotic consumption is exceptionally common.</p><p><strong>Objectives: </strong>We characterized the effects of antibiotics commonly used by Peruvian children (i.e. amoxicillin, azithromycin, cefalexin, trimethoprim/sulfamethoxazole) on the α-diversity, β-diversity and abundance of gut genera and antibiotic resistance genes (ARGs) from 3 to 16 months.</p><p><strong>Methods: </strong>This study included 54 children from a prospective cohort of enteric infections in peri-urban Lima, 2016-19. Stools collected at 3, 6, 7, 9, 12 and 16 months underwent DNA extraction and short-read metagenomic sequencing. We profiled the taxonomy of stool metagenomes and assessed ARG abundance by aligning reads to the ResFinder database. We used daily surveillance data (40 662 observations) to tabulate the number of antibiotic courses consumed in the 30 days prior to stool sampling. Using linear mixed models, we examined associations of recent antibiotic use with richness, diversity and abundance of gut genera and ARGs over time.</p><p><strong>Results: </strong>Each additional recent antibiotic course decreased Bifidobacterium and Dialister abundance and increased Veillonella abundance, although gut richness and diversity were not affected. Recent use of amoxicillin, azithromycin, cefalexin or trimethoprim/sulfamethoxazole, specifically, did not impact gut microbiome measures. Amoxicillin, azithromycin and trimethoprim/sulfamethoxazole significantly enriched multiple ARGs and amoxicillin use significantly increased total ARGs.</p><p><strong>Conclusions: </strong>Common antibiotics like amoxicillin and azithromycin appear to be key drivers of the paediatric gut resistome. Resistome perturbations appeared to be stronger, or persist for longer, than gut microbiome effects in this middle-income country setting.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of HIV-1 DNA resistance evolution in highly treatment-experienced and multi-resistant individuals under suppressive antiretroviral therapy: a longitudinal study from the PRESTIGIO Registry.","authors":"D Armenia, G Marchegiani, V Spagnuolo, M C Bellocchi, L Galli, T Clemente, L Carioti, R Lolatto, M Ferrara, R Gagliardini, G C Marchetti, C Torti, G De Socio, C Fornabaio, M Zazzi, A Castagna, M M Santoro","doi":"10.1093/jac/dkaf349","DOIUrl":"https://doi.org/10.1093/jac/dkaf349","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to clarify whether resistance detected in HIV-1 DNA might evolve in virologically suppressed highly treatment-experienced (HTE) individuals with multidrug resistance (MDR).</p><p><strong>Methods: </strong>Twenty-three virologically suppressed HTE MDR individuals from the PRESTIGIO Registry with two longitudinal samples available under virological suppression at two different time points (T0-T1) were analysed. HIV-1 DNA levels were quantified using droplet digital PCR, and resistance was assessed through next-generation sequencing (NGS) set at 5%. Mutational load was also evaluated.</p><p><strong>Results: </strong>At T0, individuals had been virologically suppressed for a median time of 3 years (IQR 3-5) under a salvage regimen, mostly containing dolutegravir (95.7%) and/or darunavir (69.6%). The median HIV-1 DNA level was 2588 copies/106 CD4+ cells at T0 and remained stable at T1 (2322 copies/106 CD4+ cells; P = 0.831). Individuals with at least ≥3-class resistance in HIV-1 DNA were 20 (87.0%) at T0 and 18 (78.2%) at T1 (P = 0.607). In those receiving NNRTI-sparing treatment (52.2%), the number of NNRTI major resistance mutation (MRM) significantly decreased over time (T0, 2 [1-3]; T1, 0 [0-1]; P = 0.027). No significant temporal differences in the number of PI, NRTI and integrase strand transfer inhibitor (INSTI) MRM were found. Specific MRM, such as M184V, decreased over time, particularly in individuals who were receiving a 3TC-/FTC-sparing salvage regimen or with a T0 mutational load of <1000 copies/106 CD4+ cells.</p><p><strong>Conclusions: </strong>Over a year, HIV-1 DNA MRM generally remained unchanged in suppressed HTE MDR people with HIV (PWH) except for a significant decline in M184V and a reduction of NNRTI resistance in the absence of NNRTI pressure.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antagonistic interaction between posaconazole and olorofim in a murine model of invasive pulmonary aspergillosis.","authors":"Christopher A Darlow, Nicola Farrington, Anne-Grete Märtson, Adam Johnson, Laura McEntee, Iona Horner, Adam Stevenson, Ana Jimenez-Valverde, Jennifer Unsworth, Shampa Das, William Hope","doi":"10.1093/jac/dkaf355","DOIUrl":"https://doi.org/10.1093/jac/dkaf355","url":null,"abstract":"<p><strong>Background: </strong>Olorofim is a new antifungal agent with a novel mechanism of action with in vitro activity against Aspergillus fumigatus and other clinically important moulds. As antifungal combinations are of interest to extend the spectrum of coverage and improve antifungal activity, we investigated the pharmacodynamics of olorofim in combination with posaconazole.</p><p><strong>Methods: </strong>Using galactomannan as a pharmacodynamic endpoint, olorofim and posaconazole were assessed alone and in combination in a neutropenic murine model of pulmonary aspergillosis using wild-type and triazole-resistant strains of A. fumigatus. Pharmacokinetic and pharmacodynamic data were fitted to a pharmacodynamic interaction model. Monte Carlo simulations of human-like regimens of both agents alone and in combination were performed to extrapolate to clinical settings.</p><p><strong>Results: </strong>With the triazole-susceptible isolate, both monotherapy arms suppressed galactomannan, but suppression with the combination was less than expected from the monotherapy arms. With the triazole-resistant isolate, monotherapy produced galactomannan suppression with olorofim but not posaconazole; the combination arm produced less suppression than olorofim alone. The interaction model revealed antagonistic pharmacodynamic interaction parameter values. Extrapolations to human pharmacokinetics predicted that combination therapy would still have a net beneficial effect in A. fumigatus infections, albeit with reduced efficacy in infections with triazole-resistant isolates.</p><p><strong>Conclusions: </strong>Posaconazole reduces the effect of olorofim in vivo. A combination of olorofim and a mould-active triazole is likely efficacious in wild-type infections but may be suboptimal in triazole resistance infections where there is minimal contribution of the mould-active triazole to antifungal activity and the triazole antagonises olorofim to produce a submaximal effect.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of eravacycline in difficult-to-treat (DTR) Acinetobacter baumannii bacteraemia in ICU: a case report.","authors":"Monica Melchio, Federica Portunato, Antonio Vena, Elisa Porcile, Monica Centanaro, Matteo Bassetti","doi":"10.1093/jac/dkaf347","DOIUrl":"https://doi.org/10.1093/jac/dkaf347","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics and dosing optimization of cefoselis in paediatric patients with haematological malignancies.","authors":"Jing-Rui Liu, Shu-Meng Fu, Totsapol Jirasomprasert, Bo-Hao Tang, Zi-Xuan Guo, Bu-Fan Yao, Yi Zheng, Guo-Xiang Hao, John van den Anker, Wei Zhao, Yue-E Wu, Ji-Zhao Gao, Zhen-Hai Shang","doi":"10.1093/jac/dkaf363","DOIUrl":"https://doi.org/10.1093/jac/dkaf363","url":null,"abstract":"<p><strong>Background: </strong>Cefoselis is a fourth-generation cephalosporin primarily indicated for infections caused by susceptible bacteria. The pharmacokinetic (PK) characteristics, efficacy and safety of cefoselis in paediatric patients with haematological malignancies remain unclear, posing a risk of suboptimal exposure and associated therapeutic failure or toxicity. Therefore, we studied cefoselis pharmacokinetics (PK) to optimize dosing in paediatric patients with haematological malignancies.</p><p><strong>Methods: </strong>Blood samples were collected from paediatric patients with haematological malignancies. A population PK (PopPK) analysis was performed using NONMEM (v7.4). Monte Carlo simulations were used to evaluate current dosing regimens by calculating the PTA. Pharmacodynamic target was defined as unbound plasma concentrations above the MIC throughout the entire dosing interval. Clinical efficacy and safety data were collected.</p><p><strong>Results: </strong>A total of 96 samples from 53 patients were collected. A two-compartment model with zero-order input and first-order elimination best described the PK of cefoselis after IV administration. Weight was the only covariate that affected PK. Monte Carlo simulations showed that the PTA was more than 96.7% for susceptible pathogens (MIC = 0.25 mg/L) at 40 mg/kg, and less than 30.5% for Pseudomonas aeruginosa (MIC = 32 mg/L) at 80 mg/kg. A total of 39 patients had body temperatures below 37.3°C after 3 ± 1 days of cefoselis treatment (with a median baseline temperature of 38.5°C). There were no adverse events leading to discontinuation.</p><p><strong>Conclusions: </strong>A PopPK model of cefoselis in paediatric patients with haematological malignancies was established and the dosing regimens were evaluated.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}